A latex agglutination immunoassay method (LAIA method) was developed by J. M. Singer et al. (see, Am. J. Med., 21888 (1956)). In the LAIA method, a dispersion (latex reagent) is obtained by dispensing an immunologically active material such as antibody disposed on fine particles of polystyrene in a liquid medium such as water with a material having a selective reactivity (such as antibody) to said immunologically active material producing an agglutinated body. The agglutinated state is observed visually, thereby noting the presence of the material to be observed. Since then, various studies have been made in connection with this method. Although quantitative determination is difficult, said method of recognizing the presence of an objective material by observing the agglutinated state of such agglutinated body visually has been widely used, since the method is simple and provides a rapid result.
In order to obtain a precise result, an attempt was made to observe the degree of agglutination of the agglutinated body by an optical measuring means.
For example, A. Fature et al. proposed a method of optically observing a change in the turbidity caused by agglutination reaction and performing quantitative determination of an objective material based on the dynamic analysis (see, Protides Biol. Fluids, Proc. Colloq., 2589 (1972)). This method is, however, problematic in that the values obtained will vary considerably because of the instability of a latex reagent used and because the method is not sufficiently sensitive. More particularly with respect to the method of A. Fature et al., the latex reagent used consists of solid fine particles dispersed in a liquid dispersing medium and which is substantially unstable. The latex reagent presents problems in that it is likely to agglutinate and/or be reduced in its sensitivity upon storage over a long period of time. Moreover, since the dispersed state thereof will be destroyed upon cryopreservation, precautions should be taken regarding its storage in order to prevent occurrence of these problems.
In order to eliminate the above problems of the latex reagent, a proposal was made by Japanese Unexamined Patent Publication 52(1977)-117420 or 62(1987)-46262 for freeze-drying the latex reagent comprising solid fine particles dispersed in a liquid dispersing medium to maintain its storage stability. According to this proposal, there is an advantage in that the storage stability of the latex reagent is improved. However, there are still unsolved problems in that a latex reagent obtained by redispersing the dried product in a liquid dispersing medium is not always constant in agglutination reactivity and because of this, there are variations in the resulting measured data.
In view of the above, according to such known method, it is possible to qualitatively detect the presence of an objective material contained in a specimen, but it is extremely difficult to accurately and quantitatively measure said material.
There is another proposal for detecting an immunologically active material contained in a specimen by injecting an agglutinated immune reagent such as latex reagent into a capillary tube, followed by freeze-drying, mixing the resultant with a specimen in said capillary tube, reacting them to produce an agglutinated body and observing the agglutinated state of said body (see, Japanese Unexamined Patent Publication 58(1983)-73866). This method is advantageous from the viewpoint that the reagent is stably maintained upon storage and the procedures are simple. However, this method is still problematic in that the reproducibility of a measured value is not sufficient and it is difficult to perform precise quantitative determination of an objective material contained in a specimen.